Publications72

..It is certain that there are many genetic factors in schizophrenia and bipolar disorder; what is needed is a complete and precise description of the contribution of each individual factor to the pathophysiology of these illnesses...

..Polymorphisms in the core promoter of the gene are associated with schizophrenia and also with diminished inhibition of the P50 response. These genetic data may identify a new pathophysiologic target for drug discovery...

..The agent 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A) is a partial alpha(7)-nicotinic agonist and can be taken orally. A phase 1 trial showed evidence for cognitive enhancement in schizophrenia...

Schizophrenia

Robert FreedmanInstitute for Children s Mental Disorders, University of Colorado and the Veterans Affairs Medical Center, Denver, USAN Engl J Med 349:1738-49. 2003

Characterization of allelic variants at chromosome 15q14 in schizophrenia

..The alpha7-receptor is a ligand-gated ion channel that admits calcium ions into cells, and it has been proposed to have various developmental roles. Its malfunction may be part of the developmental pathogenesis of schizophrenia...

..In view of these findings, the current investigation tested the hypothesis that neurocognitive performance of schizophrenia probands can predict the neurocognitive performance of their unaffected family members...

..005, allele p=0.015), and in Caucasians (genotype p=0.015, allele p=0.009). We conclude that the presence of the 2 bp polymorphism at the CHRFAM7A locus may have a functional significance in schizophrenia...

Multi-site studies of acoustic startle and prepulse inhibition in humans: initial experience and methodological considerations based on studies by the Consortium on the Genetics of Schizophrenia

..Genetic studies now often employ multiple, geographically dispersed test sites to accommodate the need for large and complex study samples. Here, we assessed the feasibility of using PPI in multi-site studies...

Comparison of polymorphisms in the alpha7 nicotinic receptor gene and its partial duplication in schizophrenic and control subjects

..Twenty-one variants were found in the exons, but non-synonymous changes were rare. Although the expression of CHRNA7 is decreased in schizophrenia, the general structure of the remaining receptors is likely to be normal...

Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes

..Relatives of childhood-onset and adult-onset probands had similar impairments. Gain and frequency of leading saccades may be genetic endophenotypes in childhood-onset and adult-onset schizophrenia...

P50 sensory gating in adolescents from a pacific island isolate with elevated risk for schizophrenia

..P50 sensory gating deficits have been found repeatedly in schizophrenic patients and in their unaffected first-degree relatives. P50 sensory gating has not yet been studied in high-risk (HR) offspring nor in prodromal adolescents...

Ventral striatal blood flow is altered by acute nicotine but not withdrawal from nicotine

..The lack of a main effect on withdrawal, but correlation of thalamic blood flow with withdrawal symptoms suggests that more complex mechanisms mediate the subjective features of the withdrawal state...

Research review: Cholinergic mechanisms, early brain development, and risk for schizophrenia

..In addition, session-dependent changes in activation were greater in some regions than others and may indicate areas of brain, such as the supplementary eye fields, that are sensitive to attentional modulation of eye movements...

..These results suggest that REM sleep is an appropriate state during which to assess P50 gating in order to disentangle the effects of state and trait on sensory gating impairment in other clinical populations...

The Consortium on the Genetics of Endophenotypes in Schizophrenia: model recruitment, assessment, and endophenotyping methods for a multisite collaboration

..The early appearance and complex, prolonged pattern of development of the alpha7 receptor suggest that it may influence processes as diverse as cell migration, dendritic elaboration and apoptosis during hippocampal maturation...

..However, auto-detrending (selecting the best algorithm or none, if detrending is not useful) appears to be the most judicious choice, particularly for analyzing fMRI data with weak activations in the presence of baseline drift...

..These results confirm previous findings of antisaccade deficits in schizophrenia subjects and support the use of the antisaccade task as a potential schizophrenia endophenotype in multi-site genetic studies...

Exacerbation of schizophrenia by varenicline

Robert FreedmanAm J Psychiatry 164:1269. 2007

Neuronal dysfunction and schizophrenia symptoms

Robert FreedmanAm J Psychiatry 164:385-90. 2007

The costs of drugs for schizophrenia

Robert FreedmanAm J Psychiatry 163:2029-31. 2006

Heritability and reliability of P300, P50 and duration mismatch negativity

..Event-related potentials (ERPs) have been suggested as possible endophenotypes of schizophrenia. We investigated the test-retest reliabilities and heritabilities of three ERP components in healthy monozygotic and dizygotic twin pairs...

The choice of antipsychotic drugs for schizophrenia

Robert FreedmanN Engl J Med 353:1286-8. 2005

Genomewide linkage scan of 409 European-ancestry and African American families with schizophrenia: suggestive evidence of linkage at 8p23.3-p21.2 and 11p13.1-q14.1 in the combined sample

..3-p15.2, 5p15.2-q13.3, 10p15.3-p14, 10q25.3-q26.3, and 11p13-q23.3. The highest increase in Z(lr) scores was observed for 5p14.1-q12.1, where the maximum Z(lr) increased from 2.77 initially to 3.80 after fine mapping in the EA families...

No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics

..Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection...

Genomewide association for schizophrenia in the CATIE study: results of stage 1

..Similar to schizophrenic patients, DBA/2 mice spontaneously exhibit a deficit in inhibitory processing of the P20-N40 auditory evoked potential, which is thought to be a rodent analog of the human P50 auditory evoked potential...

..These data are consistent with biological activity at a pathophysiological mechanism in schizophrenia and support further trials of this drug as a possible therapeutic for neurocognitive deficits in schizophrenia...

Cannabis, inhibitory neurons, and the progressive course of schizophrenia